Mast cells have been shown to release extracellular vesicles (EVs) in vitro. However, EV‐mediated mast cell communication in vivo remains unexplored. Primary mast cells from GFP‐transgenic and wild type mice, were grown in the presence or absence of lipopolysaccharide (LPS), and the secreted EVs were separated from the conditioned media. Mast cell‐derived EVs were next cultured with LPS‐naïve mast cells, and the induction of TNF‐α expression was monitored. In addition, primary mast cells were seeded in diffusion chambers that were implanted into the peritoneal cavities of mice. Diffusion chambers enabled the release of GFP+ mast cell‐derived EVs in vivo into the peritoneal cavity. Peritoneal lavage cells were assessed for the uptake of GFP+ EVs and for TNF‐α production. In vitro, LPS‐stimulated mast cell‐derived EVs were efficiently taken up by non‐stimulated mast cells, and induced TNF‐α expression in a TLR4, JNK and P38 MAPK dependent manner. In vivo, using implanted diffusion chambers, we confirmed the release and transmission of mast cell‐derived EVs to other mast cells with subsequent induction of TNF‐α expression. These data show an EV‐mediated spreading of pro‐inflammatory response between mast cells, and provide the first in vivo evidence for the biological role of mast cell‐derived EVs.
Previously it was assumed that nerve fibres are involved in the neurogenic inflammation induced by mechanical or chemical irriations. It has been also suggested that in diabetes mellitus the unmyelinated small diameter fibers are impaired as a result of diabetic neuropathy. Therefore, our aim was to study the alterations of the nerve processes in the gingivomucosal tissue in streptozotocin (STZ)-diabetic rats. Light- and electronmicroscopical examinations were made to analyze the changes in nerve fibres. After one week of steptozotocin treatment, the gingivomucosal tissue had inflammatory cell infiltration and some degenerated nerve fibres were also observed. Dense mitochondria, disorganization of cell organelles, and appearance of myelin-like dense bodies were found in the axons of degenerared nerve fibres. Semiquantitative analysis showed that 14 +/- 4% of the unmyelinated nerve fibres degenerated after one week of STZ treatment. However, degeneration of the myelinated nerve fibers was not observed. Two weeks after STZ treatment, most of the unmyelinated and myelinated nerve fibers showed degeneration (86 +/- 5%) and the placement of the ligature revealed a non-inflammatory connective tissue adjacent to a normal epithelium. The myelin sheath was disrupted and dark axoplasm with cytolysosomes became manifest. These findings demonstrated that both unmyelinated and myelinated nerve fibers are altered and inflammatory reaction exists in the gingivomucosal tissue only in the early stage of diabetes mellitus.
In this work two types of biodegradable polysuccinimide-based, electrospun fibrous membranes are presented. One contains disulfide bonds exhibiting a shorter (3 days) in vivo biodegradation time, while the other one has alkyl crosslinks and a longer biodegradation time (more than 7 days). According to the mechanical measurements, the tensile strength of the membranes is comparable to those of soft the connective tissues and visceral tissues. Furthermore, the suture retention test suggests, that the membranes would withstand surgical handling and in vivo fixation. The in vivo biocompatibility study demonstrates how membranes undergo in vivo hydrolysis and by the 3rd day they become poly(aspartic acid) fibrous membranes, which can be then enzymatically degraded. After one week, the disulfide crosslinked membranes almost completely degrade, while the alkyl-chain crosslinked ones mildly lose their integrity as the surrounding tissue invades them. Histopathology revealed mild acute inflammation, which diminished to a minimal level after seven days.
Hernia is a defect of the abdominal wall. Treatment is principally surgical mesh implantation. Non-degradable surgical meshes produce numerous complications and sideeffects such as inflammatory response, mesh migration and chronic pain. In contrast, the biodegradable, poly (vinyl alcohol) (PVA) based polymers have excellent chemical, mechanical and biological properties and after their degradation no chronic pain can be expected. The toxicology of PVA solution and fibers was investigated with Human dermal fibroblast-Adult cell line. Implantation tests were observed on long-term contact (rat) and large animal (swine) models. To measure the adhesion formation, Diamond and Vandendael score were used. Macroscopical and histological responses were graded from the samples. In vitro examination showed that PVA solution and fibers are biocompatible for the cells. According to the implantation tests, all samples were integrated into the surrounding tissue, and there was no foreign body reaction. The average number of adhesions was found on the non-absorbable suture line. The biocompatibility of the PVA nanofiber mesh was demonstrated. It has a non-adhesive, non-toxic and good quality structure which has the potential to be an alternative solution for the part of the hernia mesh.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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